In Vivo-Acquired Resistance to Daptomycin during Methicillin-Resistant Staphylococcus aureus Bacteremia

Autor: Adeline Boutet-Dubois, Chloé Magnan, Alexi Lienard, Cassandra Pouget, Flavien Bouchet, Hélène Marchandin, Romaric Larcher, Jean-Philippe Lavigne, Alix Pantel
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Antibiotics, Vol 12, Iss 12, p 1647 (2023)
Druh dokumentu: article
ISSN: 2079-6382
DOI: 10.3390/antibiotics12121647
Popis: Daptomycin (DAP) represents an interesting alternative to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Different mechanisms of DAP resistance have been described; however, in vivo-acquired resistance is uncharacterized. This study described the phenotypic and genotypic evolution of MRSA strains that became resistant to DAP in two unrelated patients with bacteremia under DAP treatment, in two hospitals in the South of France. DAP MICs were determined using broth microdilution method on the pairs of isogenic (DAP-S/DAP-R) S. aureus isolated from bloodstream cultures. Whole genome sequencing was carried out using Illumina MiSeq Sequencing system. The two cases revealed DAP-R acquisition by MRSA strains within three weeks in patients treated by DAP. The isolates belonged to the widespread ST5 (patient A) and ST8 (patient B) lineages and were of spa-type t777 and t622, respectively. SNP analysis comparing each DAP-S/DAP-R pair confirmed that the isolates were isogenic. The causative mutations were identified in MprF (Multiple peptide resistance Factor) protein: L826F (Patient A) and S295L (Patient B), and in Cls protein: R228H (Patient B). These proteins encoded both proteins of the lipid biosynthetic enzymes. The resistance to DAP is particularly poorly described whereas DAP is highly prescribed to treat MRSA. Our study highlights the non-systematic cross-resistance between DAP and glycopeptides and the importance of monitoring DAP MIC in persistent MRSA bacteremia.
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